Endocrine Disrupting Chemicals 2012 - World Health Organization

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3. Endocrine systems and endocrine disruption Figure 2. Overview of the endocrine system. Figure shows endocrine glands and some examples of hormones produced. For the purposes of this report, we have adopted the definition of an endocrine disruptor that was used in the IPCS (2002) document on endocrine disruptors (see textbox). Simplified, this means that endocrine disruptors are chemicals, or chemical mixtures, that interfere with normal hormone action. To understand endocrine disruption, we must understand the basic features of the endocrine system, which consists of many interacting tissues that talk to each other and the rest of the body using signalling mediated by molecules called hormones. The human endocrine system is visualized in Figure 2. It is responsible for controlling a large number of processes in the body, including early processes, such as cell differentiation during development and organ formation, as well as most tissue and organ functions throughout adulthood (Figure 3). A hormone is a molecule produced by an endocrine gland that travels through the blood to produce effects on distant cells and tissues via integrated complex interacting signalling pathways usually involving hormone receptors. There are over 50 different hormones and hormone-related molecules (cytokines and neurotransmitters) in humans that integrate and control normal body functions across and between tissues and organs over the lifespan. This is also the case in wildlife. Hormones and their signalling pathways are critical to the normal functioning of every tissue and organ in both vertebrates and invertebrates and are often quite similar across species. Hypothalamus Production of antidiuretic hormone (ADH), oxytocin and regulatory hormones Pituitary Gland Adenohypophysis (anterior lobe): Adrenocorticotropic hormone, Thyroid stimulating hormone, Growth hormone, Prolactin, Follicle stimulating hormone, Luteinizing hormone, Melanocyte stimulating hormone, Neurohypophysis (posterior lobe): Release of oxytocin and ADH Pineal Gland Melatonin Definition of EDCs (IPCS, 2002) Thyroid Gland Thyroxine Triiodothyronine Calcitonin Thymus (Undergoes atrophy during childhood) Thymosins Adrenal Glands Each suprarenal gland is subdivided into: Suprarenal medulla; Epinephrine Norepinephrine Suprarenal cortex: Cortisol, corticosterone, aldosterone, androgens Testis Parathyroid Glands (on posterior surface of thyroid gland) Parathyroid hormone Heart Atrial natriuretic peptide Kidney Erythropoietin Calcitriol Renin Gastrointestinal Tract Ghrelin, cholecystokinin, glucagon-like peptide, peptide YY Adipose Tissue Leptin, adiponectin, others Pancreatic Islets Insulin, glucagon Gonads Testes (male): Androgens (especially testosterone), inhibin Ovaries (female): Estrogens, progestins, inhibin “An endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub) populations.” “A potential endocrine disruptor is an exogenous substance or mixture that possesses properties that might be expected to lead to endocrine disruption in an intact organism, or its progeny, or (sub) populations.” Ovary 4 State of the Science of Endocrine Disrupting Chemicals – 2012
Early prenatal Mid- Late prenatal Postnatal Central nervous system (3 weeks - 20 years) Ear (4-20 weeks) Kidneys (4-40 weeks) Heart (3-5 weeks) Limbs (4-8 weeks) Immune system (8-40 weeks: competence and memory birth -10 years) Skeleton (1-12 weeks) Lungs (3-40 weeks: Alveolar phase birth -10 years) Reproductive system (7-40 weeks: maturation in puberty) Week 1-16 Week 17-40 Birth - 25 years Figure 3. Sensitive windows of development. Each tissue has a specific window during development when it is forming. That is the sensitive window for effects of EDCs. Notice that some tissues continue developing after birth and into infancy and childhood, providing a longer window for exposures to affect programming. Table 1. Comparison of hormone and endocrine disruptor action. Hormones Act via hormone receptors – Some have multiple receptors – Tissue-specific receptor classes and subtypes – Hormones normally bind similarly to all receptor subtypes Active at low doses – Blood levels do not always reflect activity – May be bound to serum proteins in blood with a small percentage free – No bioaccumulation Non-linear dose–response relationships – Always saturable with variable dynamic range – Can exhibit non-monotonic dose–response relationships – High-dose effects not same as low-dose effects Tissue-specific and life stage–specific effects Developmental effects permanent – Programmes brain and endocrine system for adult function Different end-points vary in sensitivity Endocrine disruptors Some act via hormone receptors and multiple receptors – Will cause abnormal receptor function – Likely isoform-specific interactions Some act at low doses, others variable – Blood levels do not always reflect activity – May be bound to serum proteins – Effects on hormone blood levels may not reflect on hormone action – Possible bioaccumulation Non-linear dose–response relationships – Always saturable with variable dynamic range – Can exhibit non-monotonic dose–response relationships – High-dose effects not same as low-dose effects Tissue-specific and life stage–specific effects Developmental effects permanent – Interferes with programming processes Different end-points vary in sensitivity Endocrine systems and endocrine disruption 5
Page 1 and 2: State of the Science of Endocrine D
Page 3: State of the Science of Endocrine D
Page 7 and 8: Preface This Summary for Decision-M
Page 9 and 10: 1. Introduction This document prese
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Page 19 and 20: 7. Why should we be concerned?—Po
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Page 29 and 30: POPs such as PCBs and DDT were bann
Page 31 and 32: suggests links between maternal pht
Page 33 and 34: Hormone-related cancers: Despite a
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Page 37 and 38: 15. References Chen D, Hale RC (201

Endocrine Disrupting Chemicals 2012 - World Health Organization

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